Quercetin, an abundant flavonol found in fruits and vegetable, has been implicated in lowering the risk of cardiovascular disease that is often associated with high plasma levels of low density ...lipoprotein (LDL) cholesterol. Here we investigated whether quercetin could modulate the expression of LDL receptors (LDLR) in HepG2 cells and the possible underlying mechanisms to exert quercetin's effects. We found that quercetin was able to induce LDLR expression with at least a 75 µ m concentration, which was accompanied by an increase in nuclear sterol regulatory element binding protein 2 (SREBP2). This effect was mediated by activation of c‐jun‐N‐terminal kinase (JNK) and extracellular signal‐regulated kinase (ERK) signalling pathways as implicated by experiments using chemical inhibitors of each pathway. When cells were challenged with protein synthesis inhibitors in quercetin‐activated LDLR transcription, LDL mRNA levels were not significantly affected by cycloheximide but puromycin abolished quercetin‐induced LDLR transcription. Taken together, we conclude that quercetin can initiate LDLR transcription by enhancing SREBP2 processing, but new protein synthesis might be necessary to exert a maximum effect of quercetin in the up‐regulation of the LDLR gene. Our findings demonstrate that quercetin strongly up‐regulated LDLR gene expression, which might elicit hypolipidemic effects by increasing the clearance of circulating LDL cholesterol levels from the blood.
•Voglibose reduced body weight, fat mass, and energy intakes in high fat fed mice.•Voglibose improved metabolic profiles and reduced circulating leptin.•Voglibose modulated genes involved in appetite ...in hypothalamus and mitochondrial function.
We tested whether long-term administration of voglibose (VO) prevents diet induced obesity in addition to hypoglycemic effects in high fat fed mice and further investigated the underlying mechanisms by which voglibose exerts its weight lowering effect. Male C57BL/6 mice were fed ad libitum for 12weeks with the control diet (CTL), high-fat diet (HFD) or the HFD with VO supplementations. Blood lipid profile, plasma leptin levels and hepatic triglyceride content, as well as expressions of genes involved in appetite and mitochondrial function were examined. The results showed that VO significantly reduced body weight, fat mass and energy intakes in high fat fed mice. VO showed improved metabolic profiles including blood glucose, triglyceride and free fatty acid. Elevated levels of plasma leptin in HFD were significantly reduced with the VO, furthermore, VO modulated the hypothalamic expressions of leptin receptors and appetite related genes. VO showed the upregulated expressions of PGC-1 in the liver and epididymal adipose tissue. In conclusion, VO may exert antiobesity properties through reductions in energy intake and improvement in mitochondrial function, indicating that VO has potential therapeutic use in patients with obesity, type 2 diabetes, and related complications.
During interaction with APCs, invariant (i) NKT cells are thought to be indirectly activated by TLR4-dependently activated APCs. However, whether TLR4 directly activates iNKT cells is unknown. ...Therefore, the expression and function of TLR4 in iNKT cells were investigated. Flow cytometric and confocal microscopic analysis revealed TLR4 expression on the surface and in the endosome of iNKT cells. Upon LPS stimulation, iNKT cells enhanced IFN-γ production, but reduced IL-4 production, in the presence of TCR signals, depending on TLR4, MyD88, TRIF, and the endosome. However, enhanced TLR4-mediated IFN-γ production by iNKT cells did not affect IL-12 production or CD1d expression by DCs. Adoptive transfer of WT, but not TLR4-deficient, iNKT cells promoted antibody-induced arthritis in CD1d(-/-) mice, suggesting that endogenous TLR4 ligands modulate iNKT cell function in arthritis. Furthermore, LPS-pretreated WT, but not TLR4-deficient, iNKT cells suppressed pulmonary fibrosis, but worsened hypersensitivity pneumonitis more than untreated WT iNKT cells, indicating that exogenous TLR4 ligands regulate iNKT cell functions in pulmonary diseases. Taken together, we propose a novel direct activation pathway of iNKT cells in the presence of TCR signals via endogenous or exogenous ligand-mediated engagement of TLR4 in iNKT cells, which regulates immune diseases by altering IFN-γ and IL-4 production.
A 5 yr old, 184 kg, and 262 cm total length female bottlenose dolphin Tursiops truncatus was found dead in a display after bloody discharge from the blowhole was observed 3 h prior to death. ...Pathological examination revealed fibrinous bronchopneumonia with prominent areas of necrosis (sequestra) and numerous Gram-negative bacilli within alveoli and in blood vessels of the lungs and liver and between muscle fibers. The cause of death was attributed to septicemia. Often, cases of fibrinous bronchopneumonia are characterized by bacteremia in the latter stages of infection, resulting in the death of the animal. Septicemia likely accounts for the ecchymoses and petechiae noted on the spleen, pancreas, forestomach, lungs, visceral peritoneum, and small intestine. Additional lesions included hemothorax, stable red frothy fluid in the trachea, and lymphoid depletion in the spleen and lymph nodes. Pure growth of Morganella morganii was isolated from the lungs, blood, liver, and blowhole mucosa. Sequencing of 16s rRNA of the isolated bacteria showed more than 99.6% identity with M. morganii strain FDAARGOS_172. To our knowledge, this is the first report of fatal fibrinonecrotizing bronchopneumonia associated with M. morganii infection in a cetacean.
This study describes a possibility for improved temperature uniformity by changing the chamber geometry using guide vane for application in test chambers. For the test chamber used in multi-chip ...testing, air cooling technology is commonly employed to maintain internal temperature and control the heat generated by semiconductor devices. The air cooling offers advantages such as simplicity of design and cost-effectiveness, however, it has the disadvantage of high dependence on fluid flow characteristics due to the shape of the internal space, making it prone to uneven airflow distribution at different locations. In order to perform especially package testing of semiconductor chips, it is necessary to actively control the target temperature in the test chamber to respond the rapidly changing temperature by heat generation of semiconductor chips. So, the accurate operation is request by the airflow control of test chamber in order to control the temperature of internal heat sources effectively. In this study, we conducted optimization research based on numerical analysis to improve temperature uniformity through efficient operation of airflow control of semiconductor package testing equipment. To analyze the accuracy of numerical analysis, we fabricated a test chamber identical to the analysis model and investigated the correlation between internal heat generation and fluid flow characteristics. It is anticipated that the validated methodology through numerical analysis and experimented research can provide a solution for achieving rapid response in attaining and maintaining the target temperature, which is essential for reducing semiconductor chip testing time to applied in an industrial context.
The electrochemical behavior of hydrogen peroxide (H
2O
2) at nanoporous platinum (Pt) thin film was investigated and the reaction of the enzymes immobilized on the electrode was examined. The ...nanoporous Pt underlying the enzyme layer was electrochemically deposited on Pt–Ir alloy microelectrodes in the solution consisting of hexachloroplatinic acid and a non-ionic surfactant, octaethylene glycol monohexadecyl ether (C
16EO
8). Glutamate oxidases were entrapped during electro-polymerization of 1,3-phenylenediamine on the nanoporous Pt microelectrodes to form a glutamate oxidase layer. The glutamate microsensors as made were compared with flat Pt-based one in terms of the performance and characteristics.
Stress is an important cause of skin disease, including hair loss. The hormonal response to stress is due to the HPA axis, which comprises hormones such as corticotropin releasing factor (CRF), ...adrenocorticotropic hormone (ACTH), and cortisol. Many reports have shown that CRF, a crucial stress hormone, inhibits hair growth and induces hair loss. However, the underlying mechanisms are still unclear. The aim of this study was to examine the effect of CRF on human dermal papilla cells (DPCs) as well as hair follicles and to investigate whether the HPA axis was established in cultured human DPCs.
CRF inhibited hair shaft elongation and induced early catagen transition in human hair follicles. Hair follicle cells, both human DPCs and human ORSCs, expressed CRF and its receptors and responded to CRF. CRF inhibited the proliferation of human DPCs through cell cycle arrest at G2/M phase and induced the accumulation of reactive oxygen species (ROS). Anagen-related cytokine levels were downregulated in CRF-treated human DPCs. Interestingly, increases in proopiomelanocortin (POMC), ACTH, and cortisol were induced by CRF in human DPCs, and antagonists for the CRF receptor blocked the effects of this hormone.
The results of this study showed that stress can cause hair loss by acting through stress hormones. Additionally, these results suggested that a fully functional HPA axis exists in human DPCs and that CRF directly affects human DPCs as well as human hair follicles under stress conditions.
•Fermented soy bean extract reduced lipid accumulation by suppressing the differentiation of 3T3-L1 adipocytes.•Fermented soy bean extract improved glucose utilization by facilitating glucose uptake ...into the adipocytes.•Fermented soy bean extract may have a potential as a functional food ingredient in improving obesity and related metabolic disorders.
Obesity is a serious health problem which may continuously increase the morbidity and mortality associated with a variety of acute and chronic diseases.This study aimed to examine the antiobesity effect of soy bean extract fermented by Bacillus subtilis MORI (BTD-1) and to elucidate the mechanisms underlying such effects using 3T3-L1 preadipocytes. Lipid accumulations were significantly inhibited by BTD-1 treatment, which were accompanied by the decreased expression of CCAAT element binding protein α (C/EBPα) and the increased phosphorylation of acetyl-CoA carboxylase (ACC) protein expression. In addition, BTD-1 treatment increased the expression of glucose transporter 4 (GLUT4) along with significantly increasing glucose uptake into the adipocytes based on results of a 2-deoxy-D-3H glucose uptake assay. Our findings suggest that BTD-1 may suppress the differentiation of 3T3-L1 adipocytes and greatly facilitate glucose uptake into the adipocytes. Therefore, BTD-1 has a potential as a functional food ingredient in improving obesity and related metabolic disorders.
The cross talk between RAGE and angiotensin II (AngII) activation may be important in the development of atherosclerosis. Soluble RAGE (sRAGE), a truncated soluble form of the receptor, acts as a ...decoy and prevents the inflammatory response mediated by RAGE activation. In this study, we sought to determine the effect of sRAGE in inhibiting AngII-induced atherosclerosis in apolipoprotein E knockout mice (Apo E KO).
9 week old Apo E KO mice were infused subcutaneously with AngII (1 µg/min/kg) and saline for 4 weeks using osmotic mini-pumps. The mice were divided into 4 groups 1. saline infusion and saline injection; 2. saline infusion and sRAGE injection; 3. AngII infusion and saline injection; 4. AngII infusion and sRAGE injection. Saline or 0.5 µg, 1 µg, to 2 µg/day/mouse of sRAGE were injected intraperitoneally daily for 28 days. We showed that atherosclerotic plaque areas in the AngII-infused Apo E KO mice and markers of inflammation such as RAGE, ICAM-1, VCAM-1, and MCP-1 were increased in aorta compared to that of the Apo E KO mice. However, the treatment of 0.5 µg, 1 µg, and 2 µg of sRAGE in AngII group resulted in the dose-dependent decrease in atherosclerotic plaque area. We also demonstrated that sRAGE decreased RAGE expression level as well as inflammatory cytokines and cell adhesion molecules in AngII or HMGB1 treated-rat aorta vascular smooth muscle cells.
The results demonstrated that partical blockade of RAGE activation by sRAGE prevent AngII -induced atherosclerosis. Therefore these results suggested that first, RAGE activation may be important in mediating AngII-induced atherogenesis, and second, AngII activation is a major pathway in the development of atherosclerosis. Taken together, results from this study may provide the basis for future anti- atherosclerotic drug development mediated through RAGE activation.
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